On May 28, 2015 Celldex Therapeutics reported the initiation of an open-label, Phase 1/2 safety and tolerability study examining the investigational combination of varlilumab and sunitinib (SUTENT) in patients with metastatic clear cell renal cell carcinoma (CC-RCC) (Press release, Celldex Therapeutics, MAY 28, 2015, View Source [SID:1234504859]). Schedule your 30 min Free 1stOncology Demo! Varlilumab is Celldex’s fully human monoclonal agonist antibody that binds and activates CD27, a critical co-stimulatory molecule in the immune activation cascade. Sunitinib is approved by the FDA as monotherapy for the treatment of advanced renal cell carcinoma (RCC), as well as certain advanced gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. Varlilumab is currently being studied in four Phase 1/2 combination studies, and additional combination studies will be initiated in 2015. Know more, wherever you are: Sunitinib blocks the function of receptor tyrosine kinases (RTKs), of which several are implicated in tumor growth, angiogenesis and metastasis. Sunitinib was selected for an investigational combination with varlilumab because it has demonstrated the potential to modulate anti-tumor immunity and reverse immune suppression in the tumor microenvironment. Varlilumab strengthens or creates an immune response against a new antigen, or target; therefore, a synergistic combination of sunitinib and varlilumab may elicit stronger responses in the immune system to fight CC-RCC and potentially other cancers. In Celldex’s Phase 1 study of varlilumab in multiple solid tumors, promising signs of clinical activity in patients with refractory CC-RCC were observed, including a durable partial response (13.0+ months) that has continued to decrease in tumor volume over time and prolonged stable disease (4 patients with a range of 5.3 to 33.0+ months).
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Latest on Antibodies in Oncology, book your free 1stOncology demo here.
"A growing understanding of renal cell carcinoma tumor biology has suggested that sunitinib’s mechanism of action may result in immune system stimulation in this indication," said Thomas Davis, M.D., Executive Vice President and Chief Medical Officer of Celldex Therapeutics. "We think we may be able to build on this potential effect in clear cell renal cell carcinoma because varlilumab can both enhance immune responses and may have a therapeutic effect through T cell signaling mechanisms. This study furthers our commitment to expanding the applicability of varlilumab across several cancers and approaches with immunotherapy in novel combinations."
The Phase 1 portion of the study will assess the safety and tolerability of varlilumab at 0.3, 1.0 and 3.0 mg/kg combined with sunitinib at 50 mg in order to identify a recommended dose for the Phase 2 portion of the study. In both phases of the trial, varlilumab will be administered once every three weeks for up to eight six-week cycles (a total of up to 16 varlilumab doses). In each six-week cycle, sunitinib 50mg will be administered orally once daily for four weeks followed by two weeks without administration. The primary objective of the Phase 2 portion of the study is to assess the preliminary anti-tumor efficacy of the varlilumab/sunitinib combination measured by the overall response rate (ORR). Secondary objectives include safety and tolerability, pharmacokinetics, immunogenicity and further assessment of anti-tumor activity across a broad range of endpoints. The study is anticipated to include up to 10 sites in the United States and enroll approximately 60 patients.
About Varlilumab
Varlilumab is a fully human monoclonal agonist antibody that binds and activates CD27, a critical co-stimulatory molecule in the immune activation cascade. CD27 can be effectively manipulated with activating antibodies to induce potent anti-tumor responses and may result in fewer toxicities due to its restricted expression and regulation. Varlilumab is a potent anti-CD27 agonist that induces activation and proliferation of human T cells when combined with T cell receptor stimulation. In lymphoid malignancies that express CD27 at high levels, varlilumab may have an additional mechanism of action through a direct anti-tumor effect. Varlilumab has completed a Phase 1 dose-escalation study, demonstrating potent immunologic activity consistent with its mechanism of action and anti-tumor activity in patients with advanced, refractory disease. No maximum tolerated dose was reached and minimal toxicities were observed. Celldex has initiated a broad development program for varlilumab to explore its role as an immune activator in combination with a number of complementary investigational and approved oncology drugs.
Author: [email protected]
MacroGenics Preclinical Research on MGD006 DART(R) Molecule Published in Science Translational Medicine
On May 27, 2015 MacroGenics reported the publication of a nonclinical research paper on MGD006 in Science Translational Medicine (Press release, MacroGenics, MAY 27, 2015, View Source [SID:1234504851]). MGD006 is a humanized, Dual-Affinity Re-Targeting (DART) molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, is expressed on malignant cells, including leukemic stem cells (LSC), in acute myeloid leukemia (AML) and other hematological diseases. The primary mechanism of action of MGD006 is its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cells. The recently published research shows anticancer activity in vitro and in mouse models together with favorable pharmacodynamic and safety profile in nonhuman primates.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The prognosis of patients with AML remains poor overall despite existing therapy, and substantial unmet need exists for these individuals. AML patients may benefit from targeted immunotherapy approaches. The paper titled "A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: Preclinical activity and safety in nonhuman primates," describes how MacroGenics’ scientists engineered the MGD006 DART and demonstrated in vitro that the molecule can arm T cells from AML patients to reduce blast counts and is effective in eliminating AML cells implanted in mice. Furthermore, MGD006 administered to cynomolgus monkeys demonstrated potent pharmacodynamic activity in the form of near complete elimination of circulating CD123-positive cells at doses that were safe and well tolerated.
"This research paved the way for our initiation of a Phase 1 clinical study of MGD006 in 2014," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "This was a significant milestone for our DART platform and I am pleased to say that the study is progressing well. MGD006 has demonstrated great promise as a T-cell re-directed cancer immunotherapy in pre-clinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome and several other forms of leukemia and lymphoma."
About the Phase 1 Study of MGD006
MacroGenics continues to enroll patients in the dose escalation portion of a Phase 1 study of MGD006 for the treatment of AML. The Phase 1 dose-escalation study is designed to assess the safety and tolerability of MGD006 in patients with relapsed or refractory AML. In addition to the primary safety endpoint, secondary endpoints of pharmacokinetics and pharmacodynamic activity will be evaluated, as will a number of biomarkers examining the immunobiology of MGD006. The Phase 1 study was initiated at Washington University School of Medicine in St. Louis. In addition, Emory University and Providence Portland Medical Center are now recruiting patients and a fourth site is expected to commence patient recruitment in June.
About MGD006
MGD006 is a humanized DART molecule that can simultaneously bind CD123 and CD3. CD123 has been reported to be overexpressed on malignant cells in a wide range of hematological malignancies including AML and myelodysplastic syndrome (MDS). AML and MDS are thought to arise in, and be perpetuated by, a small population of LSCs that generally resist conventional chemotherapeutic agents. LSCs are characterized by comparably high levels of CD123 expression in contrast to the limited or absent CD123 expression in the corresponding hematopoietic stem cell population in normal human bone marrow.
MacroGenics has retained development and commercialization rights to MGD006 in the U.S., Canada, Mexico, Japan, South Korea and India. MacroGenics’ partner, Servier, has rights to MGD006 in all other countries.
About the DART Platform
MacroGenics’ DART platform enables the targeting of multiple antigens or cells by using a single molecule with dual antibody-like binding regions. The Company has created over 100 DART molecules, which have been designed for evaluation in the potential treatment of cancer, autoimmune disorders and infectious disease. These DART molecules can be tailored for either short or prolonged pharmacokinetics and have demonstrated good stability and manufacturability. MacroGenics and its partners expect to have a total of five DART molecules in clinical development by the end of 2015.
PIQUR announces positive Phase 1 study results and the start of Phase 2 of PQR309
On May 27, 2015 PIQUR Therapeutics AG, a Swiss clinical-stage pharmaceutical company, reported positive results from the Phase 1 first-in-human study with PQR309 in advanced solid tumors (Press release, PIQUR Therapeutics, MAY 27, 2015, View Source [SID1234527275]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
PQR309 is a novel, balanced pan-class 1 PI3K/mTOR inhibitor formulated for oral administration. Preclinical studies demonstrated that PQR309 is a highly selective kinase inhibitor, penetrating blood-brain barrier with potent in vitro as well as in vivo antitumor activity.
The results from the first-in-man Phase 1 trial indicate that PQR309 is safe and well tolerated with expected pharmacokinetic profile, pharmacodynamic effect as well as clinical activity.
In total, 28 patients with advanced solid tumors were treated in cohorts of escalating PQR309 doses. The maximum tolerated dose (MTD) of PQR309 was determined to be 80 mg administered at continuous once-daily dosing schedule. Pharmacokinetic data indicate fast absorption of PQR309 as well as dose proportionality. Pharmacodynamic assessment in tumors shows downregulation of PI3K/mTOR pathway phosphoproteins.
One patient with a dysregulation of the mTOR-pathway demonstrated a confirmed partial response while another patient with a tumor containing a PI3K mutation, showed important tumor reduction and a minor response according to RECIST (Response Evaluation Criteria in Solid Tumors). "Data obtained from this first-in-human clinical study, including the evidence of clinical activity is very encouraging and highlights the clinical potential of PQR309", commented Dr. Sasa Dimitrijevic, Chief Development Officer of PIQUR.
The results of this study will be presented at ASCO (Free ASCO Whitepaper), May 29 to June 2, 2015:
"A phase 1 first-in-human (FIH) dose-escalation (DE) study of the oral dual PI3K/mTOR inhibitor PQR309 in patients (pts) with advanced solid tumors: Final DE results." [Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics, Sub-category: Signal Transduction, Abstract Number 2592, Mon, May 30, 8:00 – 11:30 AM, Location: S Hall A, Poster Board #308]
PIQUR has also received approval from the health authorities for the initiation of a Phase 2 clinical trial with PQR309, which aims to obtain efficacy data at well-tolerated doses in patients with selected solid tumor and hematological indications with aberrant PI3K/mTOR signaling. "Following recent regulatory approval to start a Phase 2 study of PQR309, we are excited to advance our compound as a potential treatment option for selected cancer indications", commented Prof. Dr. Richard Herrmann, PIQUR’s Chief Medical Officer.
Helping patients to survive cancer
PIQUR aims to help patients to survive cancer. Two out of three people are now living at least five years after their cancer has been diagnosed. Despite of significant medical innovations in the treatment of cancer, there remains a high unmet medical need for therapies that prolong patients’ survival and improve their quality of life. PIQUR targets both PI3K (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin), two key signaling molecules that are vital to several essential biological processes involved in malignant disease, such as cell proliferation, survival and metastasis, making them attractive targets in cancer therapy.
About PQR309
PIQUR’s lead compound, PQR309, is a novel, oral, balanced pan-class 1 PI3K/mTOR inhibitor with excellent prospects to become a powerful anti-cancer drug. PQR309 compares favorably to current and clinically most advanced pan-PI3K/mTOR inhibitors with respect to the drug-like properties. Unlike most of its competitors, PQR309 crosses the blood-brain barrier, expanding its use to oncologic as well as hematologic malignant diseases involving the brain. PQR309 showed activity in different aggressive cancer cell lines inhibiting the PI3K/mTOR pathway.
Halozyme, Ventana Enter Into Global Agreement To Collaboratively Develop Companion Diagnostic For Cancer Treatment
On May 27, 2015 Halozyme and Ventana Medical Systems reported a global agreement to collaborate on the development of, and for Ventana to ultimately commercialize, a companion diagnostic assay for use with Halozyme’s investigational new drug, PEGPH20 (Press release, Halozyme, MAY 27, 2015, View Source [SID:1234504843]). Schedule your 30 min Free 1stOncology Demo! The Ventana assay will be used to identify high levels of hyaluronan (HA). HA is a glycosaminoglycan – a chain of natural sugars distributed throughout human tissue – that can accumulate around cancer cells. Halozyme has announced plans for rollout of a global phase 3 clinical study in 2016 targeting metastatic pancreatic cancer patients with high HA levels using its PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Under the agreement, Ventana will develop an in vitro diagnostic (IVD), under design control, using Halozyme’s proprietary HA binding protein, with the intent of submitting it for regulatory approval in the United States, Europe and other countries.
"Ventana brings a high level of development, regulatory and commercial expertise to our companion diagnostic strategy, which will help ensure we are well prepared for the initiation of our phase 3 study in pancreatic cancer," said Dr. Helen Torley, president and CEO of Halozyme. "The agreement is an important milestone in our PEGPH20 program as we study the potential of PEGPH20 across multiple tumor types."
"We are pleased to enter into this master collaboration agreement with Halozyme, which may produce the first diagnostic to target tumor-associated HA and possibly the first companion diagnostic assay in pancreatic cancer," said Doug Ward, Vice President, Ventana Companion Diagnostics. "The PEGPH20 program, coupled with our global reach, has the potential to improve the standard of care in pancreatic cancer for patients around the world."
The financial terms of the agreement were not disclosed.
This pharma collaboration is one of many at Ventana, where the Companion Diagnostics team is developing patient stratifying diagnostic tools that can help identify those individuals who are most likely to benefit from specific treatments.
Companion diagnostics (CDx) are tests designed to confirm the presence of a specific biomarker to assist physicians in selecting effective therapies for their patients, based on the individual characteristics of each person. Incorporating a companion diagnostic strategy into a drug development program may expedite the drug approval process and help generate more effective treatments with improved safety profiles for patients.
About Ventana Medical Systems, Inc.
Ventana Medical Systems, Inc. ("VMSI") (SIX: RO, ROG; OTCQX: RHHBY), a member of the Roche Group, innovates and manufactures instruments and reagents that automate tissue processing and slide staining for cancer diagnostics. VENTANA products are used in clinical histology and drug development research laboratories worldwide. The company’s intuitive, integrated staining, workflow management platforms, and digital pathology solutions optimize laboratory efficiencies to help reduce errors, support diagnosis and enable informed treatment decisions by anatomic pathology professionals. Together with Roche, VMSI is driving Personalized Healthcare through accelerated drug discovery and the development of companion diagnostics to identify the patients most likely to respond favorably to specific therapies.
Visit www.ventana.com to learn more.
About PEGPH20
PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the systemic treatment of tumors that accumulate hyaluronan.
The FDA granted orphan drug designation to PEGPH20 for treatment of pancreatic cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreatic cancer.
Clinical trials are currently ongoing for development of PEGPH20 in pancreatic ductal adenocarcinoma and in non-small cell lung cancer. More information may be found at: View Source
Juno Therapeutics and Editas Medicine Announce Exclusive Collaboration to Create Next-Generation CAR T and TCR Cell Therapies
On May 27, 2015 Juno and Editas Medicine reported an exclusive collaboration focused on creating chimeric antigen receptor (CAR T) and high-affinity T cell receptor (TCR) therapies to treat cancer (Press release, Juno, MAY 27, 2015, View Source [SID:1234504840]). The companies will pursue three research programs together utilizing Editas’ genome editing technologies, including CRISPR/Cas9, with Juno’s CAR and TCR technologies. Schedule your 30 min Free 1stOncology Demo! "We are impressed and inspired by the scope and sophistication of Juno’s scientific vision and the exceptional product development experience of the Juno team" Know more, wherever you are: "Encouraged by the clinical results we have seen to date with our product candidates, we are committed to accessing and investing in leading science to create next generation therapeutics that maximize benefits and increase the breadth of cancers we address," said Hans Bishop, CEO, Juno Therapeutics. "Editas’ disruptive genome editing technology may unlock the ability of CAR T and TCR technologies to address a much wider range of cancers, giving hope to countless patients and families waiting for treatments."
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Latest on CAR/TCR Therapies in Oncology, book your free 1stOncology demo here.
"We are impressed and inspired by the scope and sophistication of Juno’s scientific vision and the exceptional product development experience of the Juno team," said Katrine Bosley, CEO, Editas Medicine. "They are intensely focused on advancing T cell based therapies for cancer patients, and we share their ambition to significantly expand the types of cancers that can be treated with this approach."
Under the terms of the agreement, Juno will pay Editas an upfront payment of $25 million and up to $22 million in research support over the next five years across the three programs in the alliance. Editas is also eligible to receive future research, regulatory, and commercial sales milestones in excess of $230 million for each program. Following the approval of any products resulting from the alliance, Editas is also eligible to receive tiered royalties.